TY - JOUR
T1 - Shared genetics underlying epidemiological association between endometriosis and ovarian cancer
AU - Australian Ovarian Cancer Study
AU - The International Endogene Consortium(IEC)
AU - Lu, Yi
AU - Cuellar-Partida, Gabriel
AU - Painter, Jodie N.
AU - Nyholt, Dale R.
AU - Morris, Andrew P.
AU - Fasching, Peter A.
AU - Hein, Alexander
AU - Burghaus, Stefanie
AU - Beckmann, Matthias W.
AU - Lambrechts, Diether
AU - Van Nieuwenhuysen, Els
AU - Vergote, Ignace
AU - Vanderstichele, Adriaan
AU - Doherty, Jennifer Anne
AU - Rossing, Mary Anne
AU - Wicklund, Kristine G.
AU - Chang-Claude, Jenny
AU - Eilber, Ursula
AU - Rudolph, Anja
AU - Wang-Gohrke, Shan
AU - Goodman, Marc T.
AU - Bogdanova, Natalia
AU - Dörk, Thilo
AU - Dürst, Matthias
AU - Hillemanns, Peter
AU - Runnebaum, Ingo B.
AU - Antonenkova, Natalia
AU - Butzow, Ralf
AU - Leminen, Arto
AU - Nevanlinna, Heli
AU - Pelttari, Liisa M.
AU - Edwards, Robert P.
AU - Kelley, Joseph L.
AU - Modugno, Francesmary
AU - Moysich, Kirsten B.
AU - Ness, Roberta B.
AU - Cannioto, Rikki
AU - Høgdall, Estrid
AU - Jensen, Allan
AU - Giles, Graham G.
AU - Bruinsma, Fiona
AU - Kjaer, Susanne K.
AU - Hildebrandt, Michelle A.T.
AU - Liang, Dong
AU - Lu, Karen H.
AU - Wu, Xifeng
AU - Bisogna, Maria
AU - Dao, Fanny
AU - Levine, Douglas A.
AU - Morgan, Terry K.
N1 - Publisher Copyright:
© The Author 2015.
PY - 2015/6/5
Y1 - 2015/6/5
N2 - Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
AB - Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
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U2 - 10.1093/hmg/ddv306
DO - 10.1093/hmg/ddv306
M3 - Article
C2 - 26231222
AN - SCOPUS:84943745699
SN - 0964-6906
VL - 24
SP - 5955
EP - 5964
JO - Human molecular genetics
JF - Human molecular genetics
IS - 20
ER -